Conditional ablation of C/EBP beta demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

Oncogene. 2006 Feb 23;25(8):1272-1276. doi: 10.1038/sj.onc.1209144.


The CCAAT/enhancer binding protein beta (C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre;C/EBP beta(fl/fl) mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Apoptosis*
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / physiology*
  • Carcinogens / toxicity
  • Female
  • Integrases / metabolism
  • Keratin-15
  • Keratin-5
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Keratins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Tetradecanoylphorbol Acetate / toxicity


  • CCAAT-Enhancer-Binding Protein-beta
  • Carcinogens
  • Keratin-15
  • Keratin-5
  • Krt15 protein, mouse
  • 9,10-Dimethyl-1,2-benzanthracene
  • Keratins
  • Cre recombinase
  • Integrases
  • Tetradecanoylphorbol Acetate